Chromosome band 1p36 contains a putative tumor suppressor gene important in the evolution of chronic myelocytic leukemia

被引:70
作者
Mori, N
Morosetti, R
Spira, S
Lee, S
Ben-Yehuda, D
Schiller, G
Landolfi, R
Mizoguchi, H
Koeffler, HP
机构
[1] Univ Calif Los Angeles, Sch Med, Dept Med, Div Hematol & Oncol,Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA
[2] Univ Calif Los Angeles, Sch Med, Dept Clin Pathol, Los Angeles, CA 90048 USA
[3] Univ Cattolica Sacro Cuore, Hemostasis Res Ctr, Rome, Italy
[4] Hadassah Med Org, Dept Hematol, Jerusalem, Israel
[5] Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90024 USA
[6] Tokyo Womens Med Coll, Dept Hematol, Tokyo 162, Japan
关键词
D O I
10.1182/blood.V92.9.3405.421k44_3405_3409
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Chronic myelocytic leukemia (CML) is a common neoplasm of hematopoietic pluripotent stem cells. Although the evolution from chronic phase to blast crisis (BC) in CML patients is an inevitable clinical feature, little is understood about the mechanisms responsible for the transformation. We have previously performed allelotype analysis in CML BC and have detected frequent loss of heterozygosity (LOH) on the short arm of chromosome 1. To know the common region of LOH where a putative tumor suppressor gene may reside, deletional mapping was performed using 33 microsatellite markers spanning chromosome 1 in 30 patients with CML BC (21 myeloid and 9 lymphoid). DNA was extracted from slides of bone marrow smears or from bone marrow mononuclear cells. In each patient, DNA from chronic phase was analyzed alongside DNA from either their BC or accelerated phase. Allelic loss on Ip was observed in 14 of the 30 individuals (47%): 10 of the 21 myeloid and 4 of the 9 lymphoid BC cases. Serial cytogenetic information was available in 10 cases with LOH on Ip; interestingly, deletions in this region were not detected. Two samples showed LOH at all informative loci on Ip, whereas the other 12 samples showed LOH on at least one but not all loci on Ip. The common region of LOH resided proximal to D1S508 and distal to D1S507(1p36). Our results suggest that a tumor suppressor gene that frequently plays an important role in the evolution to BC resides on 1p36 in CML. (C) 1998 by The American society of Hematology.
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页码:3405 / 3409
页数:5
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